Cat.Cat.Ca2˜Ca2˜IP3RICa2˜Ca2˜K˜CaV1.2BKCaCaMMLCK PDE5 RGS2 MYPT1 MLCP GMP pGC cGMP Hyper-polarization NucleuscGMP-A/B cGMP-A/B LZ LZ ˜˜˜°PKG1 NO sGC GTPGPCR IRAG ER Actin/myosin °˛G˜q IP3 PLC°12354 •Fig. 14.12 Signalingmechanismsbywhichnitricoxide(NO)andnitroprusside(NP)promoterelaxationofvascularsmoothmuscle.Nitricoxidestimulatessolubleguanylcyclase(sGC)inthevascularsmoothmusclecell,resultinginproductionofcGMP,activationofproteinkinaseG(PKG1),whichinturnphosphorylatesvarioussubstratesthat(1)inhibitInP3production,(2)inhibitInsP3-inducedCa++ release, (3)activatemyosinlight-chainphosphatase,(4)activatethelargeconductanceCa++-activatedK+ channel(BKCa),whichhyperpolarizesthecellandthusinhibitsthevoltage-gatedCa++ channel(Cav1.2)(5).BKCa,calcium-activatedmaxi-Kchannel;CaM,calmodulin;Cat,catalyticdomain;Cav1.2,L-typecalciumchannel;ER,endoplasmicreticulum;GPCR,Gprotein–coupledreceptor;IP3RI,inositol1,4,5-trisphosphate(IP3)receptorI;IRAG,inositoltrisphosphatereceptor-associatedcGMP-kinasesubstrate;LZ,leucine/isoleucinezipper;MLCK,myosinlight-chainkinase;MLCP,myosinlight-chainphosphatase;MYPT,regulatorymyosinphosphatasetargetingsubunit1;PDE5,phosphodiesterase5;pGC,particulateguanylylcyclase;PLCβ,phospholipaseCbeta;RGS2,regulatorofG-proteinsignaling2;sGC,solubleguanylylcyclase.(ModifiedfromSchlossmannJ,DeschM.Am J Physiol Heart Circ Physiol 2011;301:H672–H682.)
Blood flow to tissues such as the brain is maintained at a relatively constant flow over a wide range of blood pressures through a process called autoregulation. The mechanism underlying autoregulation of blood flow involves the myogenic response, wherein an increase in distending pressure in an artery results in vasoconstriction, whereas a decrease in transmural pressure results in a vasodilation (over a given range of pressures). As shown in
Fig. 14.13 , distention of the resistance artery resulted in an immediate elevation of intracellular [Ca++], followed by vasoconstriction in an effort to maintain relatively constant flow. The mechanism underlying this elevation of intracellular [Ca++] and subsequent vasoconstriction is complex. The rise in intracellular [Ca++] in response to stretch been reported to involve stretch-activated channels, InsP3-signaling, and voltage-gated Ca++ channels.
During development and growth, the number of smooth muscle cells increases (
Fig. 14.14 ). Smooth muscle tissue mass also increases if an organ is subjected to a sustained increase in mechanical work. This increase in mass is called compensatory hypertrophy. A striking example occurs with arterial smooth muscle cells (i.e., in the tunica media of the artery) in hypertensive patients. The increased mechanical load on the muscle cells appears to be the common factor that induces this hypertrophy. Chromosomal replication can result in significant numbers of polyploid muscle cells. The polyploid cells contain multiple sets of the normal number of chromosomes. They synthesize more contractile proteins and thus increase the size of the cell (see
Fig. 14.14